1. Field of the Invention
The present invention relates to a method of making blood-compatible, antimicrobial surfaces.
2. Description of the Related Art
Microbial growth can pose serious threats to human health. Microbes able to grow on the surfaces of medical articles can put patients at risk for developing uncontrollable infections. Increasing numbers of antibiotic resistant microbes are creating an urgent need to develop methods of inhibiting microbial growth on surfaces.
The rapidly growing biotechnology industry is especially sensitive to the dangers of microbial contamination and growth. In the laboratory, uncontrolled microbial growth can contaminate experiments and ruin their results. In a pharmaceutical plant, unwanted microbial growth in a reactor can taint drugs and disrupt production.
Microbial growth can also cause damage to our food and water supplies. Foods that are not properly stored in microbe free containers will quickly spoil, and perhaps even become poisonous. Pathogenic microbes found in raw foods, especially meats, spread on the surfaces of food handling articles creating a health hazard. Such food handling articles include utensils, dishes, glasses, bowls, cutting surfaces, and counter tops. Microbial growth in our water supplies not only threatens public health, but also clogs the pipes, pumps, and water treatment plants used to deliver safe drinking water.
Microbial growth on the surfaces of articles touched by many people promotes the spread of infectious diseases. Mundane articles such as seats, telephones, doorknobs, handles, latches, railings, and especially sinks and toilets, would be more sanitary if their surfaces were made to inhibit microbial growth.
There have been previous attempts to inhibit microbial growth on surfaces. Lacquer-like coatings containing quaternary ammonium salts have been applied as antimicrobial coating on surfaces (S. E. Tebbs and T. S. J. Elliott . J. Microbiol. Chemoth. 31 (1993). 261-271 the content of which is hereby incorporated by reference). Lacquers of silver salts have also been used for antimicrobial coatings (International Patent Application WO 92/18098. Unfortunately, the salts in these coatings are water soluble, and are quickly washed out of the coating by perspiration and other bodily fluids. Once the salts are removed, the coating looses its antimicrobial properties.
There have been attempts to chemically bond bactericidal active compounds on polymer surfaces (T. Ouchi and Y. Ohya, Progr. Polym. Sci. 20 (1995), 211. et seq,. Unfortunately, the chemical bonding of the antimicrobial compound to the polymer usually reduces its antimicrobial activity. Moreover, microbial debris has been found to build up on the surface of these treated polymers, eventually forming a layer thick enough to support new microbial growth.
It has been reported that polyurethane film can be treated to resist the microbe Staphylococcus epidermidis. The film is first pretreated with a glow discharge in the presence of oxygen, and then acrylic acid is grafted onto the film (W. Kohnen et al., ZBI. Bakt. Suppl. 26, 1994, pp. 408-410, Gustav Fischer Verlag, Stuttgart-Jena-New York.
In addition to being susceptible to microbial contamination, medical articles used as implants can cause dangerous blood clots. The clots are started when blood cells and other blood particles, such as thrombocytes, adhere to the surface of the implanted device. While certain disinfectants (e.g. benzalkonium chloride/heparin) have been shown to reduce the incidence of clotting, they have poor adherence to the underlying substrate, and quickly dissolve off the surface of the implanted device.
It has been reported that membranes treated with a low pressure plasma are less likely to cause blood clotting, i.e. be thrombogenic, than similar, untreated membranes (International Patent Application WO 94/17904. In the description of the treatment method, SO.sub.2 was mentioned as a suitable plasma forming gas.
There have been additional reports on using SO.sub.2 as a plasma forming gas in the plasma treatment of LDPE tubes (J. C. Lin et al., Biomaterials 16 (1995), 1017-1023. The authors reported that the surfaces modified by SO.sub.2 plasma treatment were strongly hydrophilic, and more thrombogenic than untreated surfaces. They attributed this result to the addition of polar sulfonate groups, created by the SO.sub.2 plasma treatment, to the already hydrophilic surface of the LOPE tubes.